The basis for pathogenicity of E histolytica

Adherence and chemotaxis

Entamoeba histolytica extracellular killing of host cells is contact dependent. Adherence to human colonic epithelial cells and mucins is mediated by a galactose-specific Gal/GalNAc lectin (Saffer and Petri 1991). Galactose-specific binding of the soluble adherence lectin has been extensively studied, and anti-lectin antibodies have been used to develop an assay for the identification of E. histolytica in stools (see subsequently). Monoclonal antibodies to the extracellular cysteine-rich region of the 170-kDa subunit have been shown to interfere with adhesion to target cells (Mann and Lockhart 1998). Fibronectin fragments also appear to stimulate directed trophozoite migration and chemokinesis (Franco et al. 1997). Adherence of E. histolytica to target cells by means of the described surface lectin induces a cytolytic response involving secretion of proteolytic substances and pore-forming peptides.

Penetration, invasion, and cytolysis

Entamoeba histolytica virulence is related to a number of amoebic components (lectins, cysteine proteinases, and lytic peptides), the intestinal bacterial flora, as well as other host factors. Invasive amoebas resist lysis by serum complement in contrast to non-invasive ones. Trophozoites are selective in their interactions with bacteria, and the parasite recognition of glycoconjugates plays an important role in amoebic virulence (Padilla-Vaca et al. 1999).

Active migration of E. histolytica trophozoites through extracellular matrices might play a role in host tissue destruction. Trophozoites degrade fibronectin bound to their surface and adhere to substrate-bound fibronectin, producing local matrix degradation. Tissue invasion has been linked to amoeba collagenase production, and especially degradation of collagen type I (see Ravdin 1988). Cytopathic and cytolytic activities of viable trophozoites against mammalian nucleated cells and red blood cells have been extensively studied. Cytolytic peptides of E. histolytica capable of formation of ion channels in target cell membranes exist in amoebic cytoplasmic granules. They have been described as amoebapores lysing several types of mammalian cells and as hemolysins based on their lytic effect on erythrocytes (Jansson et al. 1994). Amoebapores, 77-residue peptides, are structural and functional analogues of NK-lysin and granulysin of porcine and human cytotoxic lymphocytes. These peptides may be related to members of the gene family of saposin-like proteins having antibacterial activity (Banyai and Patthy 1998). They have been proposed to be major pathogenicity factors of E. histolytica (Bracha et al. 1999). That differences in abundance and activity of the lytic polypeptides may have an impact on the pathogenicity of amoebae is suggested by the comparison between amebapores of E. histolytica and E.

dispar (Nickel et al. 1999).

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